Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors

• Published in: Clinical immunology (Orlando, Fla.) Vol. 166-167; pp. 48 - 58
• Main Authors: Murahashi, Mutsunori, Hijikata, Yasuki, Yamada, Kazunari, Tanaka, Yoshihiro, Kishimoto, Junji, Inoue, Hiroyuki, Marumoto, Tomotoshi, Takahashi, Atsushi, Okazaki, Toshihiko, Takeda, Kazuyoshi, Hirakawa, Masakazu, Fujii, Hiroshi, Okano, Shinji, Morita, Masaru, Baba, Eishi, Mizumoto, Kazuhiro, Maehara, Yoshihiko, Tanaka, Masao, Akashi, Koichi, Nakanishi, Yoichi, Yoshida, Koji, Tsunoda, Takuya, Tamura, Kazuo, Nakamura, Yusuke, Tani, Kenzaburo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016
• Subjects: Adult; Aged; Aged, 80 and over; Allergy and Immunology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - immunology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Cancer Vaccines - immunology; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - immunology; Dose-Response Relationship, Drug; Drug Administration Schedule; Epitopes - administration & dosage; Epitopes - immunology; Female; Five-peptide cancer vaccine; HLA-A24 Antigen - genetics; HLA-A24 Antigen - immunology; Humans; Kaplan-Meier Estimate; Leukopenia - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Male; Middle Aged; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - immunology; Peptides - administration & dosage; Peptides - immunology; Regulatory T cells; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Translational research; Treatment Outcome; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - adverse effects; Vaccines, Subunit - immunology; CPM; Translational research; Five-peptide cancer vaccine; Cyclophosphamide; OS; TAA; CTLs; Treg cells; PFS; Regulatory T cells; cytotoxic T lymphocytes; tumor-associated antigen; progression free survival; regulatory T cells; overall survival; cyclophosphamide
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2016.03.015

We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies. •A clinical trial of multipeptide cancer vaccine with cyclophosphamide was conducted.•Eighteen patients positive for HLA-A2402 with advanced solid tumors were enrolled.•Treatment was well tolerated without any adverse events above grade 3.•Vaccine-specific T cell responses were associated with longer survival.